Production of Michellamine B by Plant Tissue Culture

Michellamine B is a potential anti-HIV agent in advanced preclinical development within the NCI.Further clinical development and trials are limited by an acute shortage of supply and no long-termsource for commercial supply has been identified. Our long-term objective is to produce MichellamineB in bulk using a plant cell-culture process. Innovative cell culture growth establishment andmaintenance, product formation and monitoring, and germplasm screening strategies will be developedin a comprehensive and integrated manner. The specific aim of Phase I research is to establish thefeasibility using plant cell cultures for Michellamine B production by accomplishing five enablingobjectives: 1) develop network for germplasm collection; 2) establish callus cultures and developmaintenance techniques; 3) refine analytical methods for the detection and quantitation of MichellamineB; 4) establish cell suspensions from callus cell lines and develop preliminary conditions favoring growthand product formation; and 5) Screen cell lines from an available germplasm pool and identify a few elitelines capable of producing Michellamine B. Technologically innovative components include i) the use ofplant cell cultures for production of pharmaceuticals, ii) the use of comprehensive optimization ofvariables for establishment and enhancement of callus and cell suspension growth, and iii) the use ofnovel rapid-screening methods for identifying productive cell lines. The research will help to form thebasis for a scalable and commercially successful route to Michellamine B production that will be superiorto other approaches.